Cabozantinib Active as Salvage Therapy in Thyroid Cancer

Jason Harris

Published: Tuesday, Sep 05, 2017

Cabozantinib (Cabometyx) demonstrated durable activity in patients with radioiodine (RAI)-refractory differentiated thyroid cancer (DTC) who progressed on VEGFR-targeted therapy, according to phase II data published in the Journal of Clinical Oncology.

The findings from the International Thyroid Oncology Group trial showed that 10 (40%) of the 25 patients enrolled in the study had a confirmed partial response (PR) and 13 (52%) had stable disease as their best response, including 2 patients with an unconfirmed PR. Two patients were not evaluable because of a lack of imaging studies.

The median time to PR was 2 months (range, 2-8), and the median duration of PR was 11.3 months (95% CI, 10.3 – not evaluable).

“Our data demonstrate that in the salvage setting, cabozantinib is effective, with an impressive rate of 40%, a median progression-free survival (PFS) of 12.7 months, and a median overall survival (OS) of 34.7 months,” the study investigators, led by Manisha H Shah, MD, professor of medicine with The Ohio State University Comprehensive Cancer Center—James, wrote. “Cabozantinib is an effective salvage therapy in patients with RAI-refractory DTC who have experienced disease progression on previous VEGFR-targeted therapies.”

From September 2013 to January 2015, investigators at 6 medical centers in the United States recruited adults with advanced thyroid cancer—papillary, follicular, Hürthle cell, or poorly differentiated—into this phase II study. Eligible patients (N = 25) had progressed after receiving up to 2 lines of prior VEGFR-targeted therapy.

The oral multikinase inhibitor cabozantinib was administered at a starting dose of 60 mg daily in 28-day cycles. Patients who tolerated the 60-mg dose with no grade ≥2 treatment-related adverse events (AEs) could have their dose increased to 80 mg daily. Patients who experienced grade ≥2 treatment-related AEs had their dose reduced to 40 mg daily, and again to 20 mg daily, if necessary. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent.

Seven patients (28%) were treated with 60 mg/day of cabozantinib. Four (16%) had a dose escalation to 80 mg daily, 6 (24%) had a dose reduction to 40 mg per day, and 8 (32%) reduced to 20 mg per day. Overall, investigators administered a total of 275 twenty-eight–day cycles of cabozantinib.

Eleven patients discontinued due to progressive disease, 9 for AEs, and 1 each for clinical progression and insurance issues. One patient died while on study. Two patients remained on cabozantinib at the time of data cutoff.

Most patients had aggressive histology (28% PDTC, 20% HTC, 16% FTC), and investigators observed a high frequency of bone (84%), liver (36%), and brain (20%) metastases. Patients had high tumor burden at baseline. Along with RAI, patients were heavily